Nine-membered Ring Research Articles

ChemInform Abstract: Concise Copper‐Catalyzed Synthesis of Tricyclic Biaryl Ether‐Linked Aza‐Heterocyclic Ring Systems.

A new method for the synthesis of tricyclic biaryl ether-linked ring systems incorporating seven-, eight-, and nine-membered ring amines is presented. In the presence of catalytic quantities of copper(I), readily accessible acyclic precursors undergo an intramolecular carbon–oxygen bond-forming reaction facilitated by a “templating” chelating nitrogen atom. The methodology displays a broad substrate scope, is practical, and generates rare and biologically interesting tricyclic heteroaromatic products that are difficult to access by other means.

Absolute configuration determination of theanti-head-to-head photocyclodimer of anthracene-2-carboxylic acid through cocrystallization withL-prolinol

The absolute configuration has been established of the enantiopure anti-head-to-head cyclodimer of anthracene-2-carboxylic acid (AC) cocrystallized with L-propinol and dichloromethane [systematic name: (S)-2-(hydroxymethyl)pyrrolidin-1-ium (5R,6S,11R,12S)-8-carboxy-5,6,11,12-tetrahydro-5,12:6,11-bis([1,2]benzeno)dibenzo[a,e][8]annulene-2-carboxylate dichloromethane monosolvate], C5H12NO(+)·C30H19O4(-)·CH2Cl2. In the crystal structure, the AC dimer interacts with L-prolinol through a nine-membered hydrogen-bonded ring [R2(2)(9)], while the dichloromethane molecule is incorporated to fill the void space. The absolute configuration determined in this study verifies a recent assignment made by comparing theoretical versus experimental circular dichroism spectra.

Concise Copper-Catalyzed Synthesis of Tricyclic Biaryl Ether-Linked Aza-Heterocyclic Ring Systems

A new method for the synthesis of tricyclic biaryl ether-linked ring systems incorporating seven-, eight-, and nine-membered ring amines is presented. In the presence of catalytic quantities of copper(I), readily accessible acyclic precursors undergo an intramolecular carbon-oxygen bond-forming reaction facilitated by a "templating" chelating nitrogen atom. The methodology displays a broad substrate scope, is practical, and generates rare and biologically interesting tricyclic heteroaromatic products that are difficult to access by other means.

Synthesis of fused nine-membered rings: a simple protocol for synthesis of [1,2,3]-triazolo-[1,4]-benzoxazonine frameworks from the Baylis–Hillman acetates

A simple and facile protocol for synthesis of tricyclic [1,2,3]-triazolo-[1,4]-benzoxazonine derivatives has been developed from the Baylis–Hillman acetates by treatment with sodium azide followed by heating the resulting azido-alkyne in toluene under reflux [Huisgen reaction (click reaction)] in the absence of any copper salt.

Biosynthetic Study of Actinomycetes-Metabolites for Creating Novel Analogs

The aminocyclitol family is a relatively new class of natural products such as gentamicin, kanamycin, and streptomycin, which have been used clinically for decades as potent antimicrobial agents. These secondary metabolites are chiefly produced by microorganisms, especially Actinomycetes. Their chemical structures most commonly contain a C7N unit, 2-epi-5-epi-valiolone or 3-amino-5-hydroxybenzoic acid (3,5-AHBA) which are known to be responsible for their biological activities. In the course of current study, the biosynthesis of the C7N-containing metabolites, validamycin and acarbose, pactamycin, have been evaluated. We studied N-formamide salicylic acid (FSA) moiety which is a C7N unit synthesized from tryptophan by microorganisms. A strong antifungal agent antimycin, isolated from several Streptomyces sp., contains an FSA moiety, and constitutes a unique nine-membered dilactone ring with L-threonine, short-chain fatty acid, and an amide linkage connecting it to an FSA moiety. Also, an antitumor antibiotic asukamycin, produced by Streptomyces nodosus subsp. asukaensis ATCC 29757, consists of both 3,4-AHBA and C5N, cyclohexane ring linked to trans-triens. To improve the efficacy and reduce the toxicity of these metabolites, further structural modification is needed. Total chemical synthesis of these complex compounds is difficult. Therefore, alternative approaches are required, e.g., biosynthetic or genetic modification methods. This review presents the biosynthetic study on these compounds for creating new analogs using mutasyntheis.

Synthesis of (−)-Epi-Indolactam V by an Intramolecular Buchwald–Hartwig C–N Coupling Cyclization Reaction

The synthetic efforts toward the concise synthesis of (-)-indolactam V from simple and commercially available starting materials using palladium- and copper-catalyzed intramolecular N-arylation strategy for the elaboration of the requisite nine-membered lactam ring as the key step are described. The incorporation of a turn-inducing structural element along the linear precursor was fundamental to achieve the heterocyclization step as well as obtain the correct regio- and chemoselectivity. The stereoselective nature in the C-N coupling cyclization reaction is interpreted in terms of minimization of allylic strain at the transition state for the palladium-amido complex formation. Meanwhile, the synthesis of the (-)-epi-indolactam V and its enantiomer have been accomplished.

Thiophene-2-carbonyl azide

The title compound, C5H3N3OS, is almost planar (r.m.s. deviation for the ten non-H atoms = 0.018 Å) and forms an extended layer structure in the (100) plane, held together via hydrogen-bonding inter­actions between adjacent mol­ecules. Of particular note is the occurrence of RC—H⋯N−=N+=NR inter­actions between an aromatic C—H group and an azide moiety which, in conjunction with a complementary C—H⋯O=C inter­action, forms a nine-membered ring.

5-Amino-1H-1,2,4-triazol-4-ium hydrogen oxalate

In the title salt, C2H5N4 +·C2HO4 −, the hydrogen oxalate anions form corrugated chains parallel to the c axis, linked by inter­molecular O—H⋯O hydrogen bonds. The 5-amino-1H-1,2,4-triazol-4-ium cations are connected into centrosymmetric clusters via weak C—H⋯N hydrogen bonds forming nine-membered rings with an R 3 3(9) motif. These clusters are inter­connected via anions through N—H⋯O hydrogen bonds, building a three-dimensional network.

Ethyl 2-(5-methoxy-2-methyl-1H-indol-3-yl)acetate

In the title compound, C14H17NO3, the nine-membered 1H-indole ring system is essentially planar [maximum deviation = 0.019 (1) Å]. In the crystal, mol­ecules are linked via N—H⋯O hydrogen bonds, forming chains along [001]. These chains are linked via C—H⋯O hydrogen bonds and C—H⋯π inter­actions, forming a two-dimensional network lying parallel to the ac plane.

ChemInform Abstract: Officinatrione: An Unusual (17S)‐17,18‐seco‐Lupane Skeleton, and Four Novel Lupane‐Type Triterpenoids from the Roots of Taraxacum officinale.

AbstractFive new lupane‐type triterpenoids, (I)‐(IV), are isolated from the root of dandelion T.

Detection of ground states in frustrated molecular rings by in-field local magnetization profiles

It is demonstrated by means of exact numerical methods that the ground state of nine-membered frustrated homometallic chromium-based molecular rings with a single bond defect can be unambiguously determined by the in-field local magnetization profiles, which exhibit characteristic patterns. The strength of the coupling corresponding to the defect can be determined by both total and local magnetization measurements on single crystals with the field perpendicular to the ring. This approach is illustrated with a recently synthesized chromium ring Cr${}_{9}$Cl${}_{2}$, which is experimentally characterized by low-temperature magnetic measurements and analyzed by means of the microscopic quantum model. The strength of the coupling corresponding to the defect is estimated by fitting the magnetic susceptibility of a powder sample and independently confirmed from the experimental intersection point of total magnetization profiles preserving the typical values of the remaining parameters, which are well established for known chromium rings.

Synthesis of monocyclic nine-membered compounds by the [4+3+2] cycloaddition-bond cleavage strategy

Monocyclic nine-membered compounds were synthesized by the cleavage of the six-membered ring of the bicyclic compounds. Thus, the bicyclic compounds which consist of six- and nine-membered rings were synthesized by the Ni-catalyzed [4+3+2] cycloaddition, and the cleavage of the N–O bond, which was incorporated in the six-membered ring, proceeded in the presence of Mo(CO)6 to yield the monocyclic compound. On the other hand, the cleavage of the C–O bond proceeded efficiently in the presence of SmI2.

Microbiological transformation of the triterpene nigranoic acid by the freshwater fungus Dictyosporium heptasporum

The microbiological transformation of the triterpene nigranoic acid (3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid) (1) to 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7β-hydroxy-16β,26-lactone-3-oic acid (2) and 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7β-hydroxy-16β-methoxy-3,26-dioic acid (3) by the freshwater fungus Dictyosporium heptasporum YMF1.01213 has been demonstrated. The structures of the biotransformation products were determined by spectroscopic and MS analyses. Compound 2, characterized by the presence of a formed C-16/C-26 ester bridge, provided a novel nine-membered lactone ring structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, Compounds 1–3 exhibited weak anti-HIV activity in vitro. Compounds 2 and 3 were reported for the first time as natural product derivatives.

Amomaxins A and B, Two Unprecedented Rearranged Labdane Norditerpenoids with a Nine-Membered Ring from Amomum maximum

Amomaxins A (1) and B (2), featuring an unprecedented rearranged labdane norditerpene skeleton with a nine-membered ring, along with their biosynthetic related known compound isocoronarin D (3) were isolated from the roots of Amomum maximum. Their structures with absolute configurations were determined by spectroscopic data, CD experimentation, and single-crystal X-ray diffraction. Compound 2 showed an inhibitory effect on nitric oxide (NO) production in lipopolysaccharide-induced RAW264.7 macrophages.

Sensitized Photooxidation of S-Methylglutathione in Aqueous Solution: Intramolecular (S∴O) and (S∴N) Bonded Species

Nanosecond laser flash photolysis was used to generate sulfur radical cations of the thioether, S-methylglutathione (S-Me-Glu), via the one-electron oxidation of this thioether by triplet 4-carboxybenzophenone. The purpose of this investigation was to follow the neighboring group effects resulting from the interactions between the sulfur radical cationic sites and nearby lone-pair electrons on heteroatoms within the radical cation, especially the electron lone-pairs on heteroatoms in the peptide bonds. The tripeptide, S-Me-Glu, offers several possible competing neighboring group effects that are characterized in this work. Quantum yields of the various radicals and three-electron bonded (both intramolecular and intermolecular) species were determined. The pH dependence of photoinduced decarboxylation yields was used as evidence for the identification of a nine-membered ring, sulfur-nitrogen, three-electron bonded species. The mechanisms of the secondary reactions of the radicals and radical cations were characterized by resolving their overlapping transient-absorption spectra and following their kinetic behavior. In particular, sulfur-oxygen and sulfur-nitrogen three-electron bonded species were identified where the oxygen and nitrogen atoms were in the peptide bonds.

Ni‐Catalyzed [4+3+2] Cycloaddition of Ethyl Cyclopropylideneacetate and Dienynes: Scope and Mechanistic Insights

A detailed study of the Ni-catalyzed [4+3+2] cycloaddition reaction between ethyl cyclopropylideneacetate and dienynes has been conducted, resulting in the development of a new method for the synthesis of compounds containing nine-membered rings. We studied the reactivity of various dienynes, together with their substituent and conformational effects. The mechanism of the reaction was probed by examining the stoichiometric reactions of the Ni complexes and dienynes.

Diversity oriented synthesis of indole-based peri-annulated compounds via allylic alkylation reactions

Diverse indole-based peri-annulated compounds were synthesized via transition-metal-catalyzed allylic alkylation reaction. With palladium catalyst, indole-based nine-membered ring products were obtained in 40–70% yields. When iridium catalyst was used, highly enantioenriched seven-membered ring products were obtained in 40–78% yields and 91–97% ee. Meanwhile, when 3-substituted indole substrates were employed with a palladium catalyst, asymmetric allylic dearomatization of indoles occurred with products obtained in 48–78% yields and 35–78% ee with a chiral ferrocene-based Phox ligand. Interestingly, with an iridium catalyst, Friedel–Crafts type allylic alkylation reaction proceeded at the C5 position of indole, affording the products with 40–60% yields and 56–97% ee.

Officinatrione: an unusual (17S)-17,18-seco-lupane skeleton, and four novel lupane-type triterpenoids from the roots of Taraxacum officinale

Novel 5 lupane-type of triterpenois, i.e., 3β-acetoxy-18α,19α-epoxylupan-21β-ol (1), 18α,19α-epoxy-21β-hydroxylupan-3-one (2), lup-18-ene-3,21-dione (3), lupa-18,21-dien-3β-yl acetate (4), and (17S)-17,18-seco-lup-19(21)-ene-3,18,22-trione (5), named officinatrione, as well as 16 known compounds from the roots of Taraxacum officinale collected in Takatsuki city, Osaka, Japan. Of the above compounds, 5 was the first lupane-type triterpene, of which the D-ring was open to form a nine-membered ring. Compounds 2 and 5 exhibited moderate cytotoxic activities against L1210 cell line (IC50 10.5 and 10.1 μM).

Total Synthesis of (–)-Lycoposerramine-S

Key words lycoposerramine-S - azomethine ylides - 1,3-dipolar cycloaddition

The Synthesis of Melohenine B and a Related Natural Product

A concise synthesis of melohenine B and O-ethyl-14-epimelohenine B, from eburnamonine, was achieved via a biomimetic diastereoselective singlet oxygen-mediated oxidative cleavage of the indole C2-C7 bond. These studies enabled the assignment of the absolute configuration of the natural products. In line with a proposed biosynthetic pathway, the resulting nine-membered ring containing products could be converted to the corresponding quinolones.